Objectives
Hyponatremia (serum sodium [Na+] concentration <136 mmol/L) is a prevalent and potentially life-threatening medical
comorbidity for schizophrenic patients. No definitive pharmacological treatments have
been established. Tolvaptan (OPC-41061), an oral non-peptide V2-receptor antagonist, was recently shown to correct hyponatremia in a diverse population
of 448 hyponatremic patients. Efficacy in a sub-set of 19 schizophrenic patients with
idiopathic hyponatremia included in that sample is specifically examined.
Methods
Nineteen subjects were randomly assigned to receive placebo (n = 12) or tolvaptan (n = 7) once daily for 30 days. Dosage adjustment was based on serum Na+ changes, initially 15 mg, titratable to 30 or 60 mg. The average daily area under
the curve (AUC) changes in serum Na+ from baseline to Day 4 and Day 30 were co-primary end points.
Results
Increases in serum Na+ concentrations were significantly greater with tolvaptan than placebo at Day 4 (p = .0055) and at Day 30 (p < .0001). Two subjects receiving tolvaptan (28.6%) became dehydrated and experienced
hypotension, and five subjects receiving placebo (41.7%) experienced symptoms associated
with dilutional hyponatremia.
Conclusions
These results suggest that tolvaptan effectively normalizes idiopathic hyponatremia
in schizophrenic patients. Clinicians are advised to carefully monitor fluid status
especially at the beginning of treatment to prevent dehydration.
Key Words
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Article info
Publication history
Published online: August 11, 2008
Accepted:
June 19,
2008
Received in revised form:
June 9,
2008
Received:
May 2,
2008
Identification
Copyright
© 2008 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.
